A POSSIBLE ROLE OF SEROTONIN IN HYPOTHALAMIC SELF-STIMULATION IN DOGS

¹ Department of Pharmacology, School of Medicine and Dentistry, University of Rochester, Rochester, New York, and The Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana

Electrodes were chronically implanted in dogs in the area of the medial mammillary nucleus of the posterior hypothalamus. These animals were trained to press a lever for electrical stimuli at various current intensities. Drugs were administered which altered the brain levels of serotonin and catecholamines. The effects of these drugs and a serotonin antagonist on the thresholds for self-stimulation response rates were measured.

The administration of -methyl dopa, which lowers the brain levels of norepinephrine, dopamine and serotonin in several species, resulted in a marked and significant depression of intracranial self-stimulation response rates in dogs. This inhibitory effect correlated better with brain levels of serotonin than of norepinephrine or dopamine.

A low dose of BOL, a serotonin antagonist, lowered the threshold for self-stimulation, and a high dose raised the threshold, in 2 of 3 animals in each case.

The administration of JB-516, a monoamine oxidase inhibitor that causes an elevation of brain serotonin levels in dogs without causing a concomitant elevation of norepinephrine levels, resulted in a lowering of threshold for self-stimulation in 2 of 3 animals.

Thus the evidence suggests that serotonin may be a neurohormone of importance in maintaining the activity of this reward system of the posterior hypothalamus. This does not preclude a role of catecholamines, and the fact that some sympathomimetic agents can affect this system under different conditions would suggest that more than one neurohormone may be involved in maintaining the activity of hypothalamic reward systems.